One of many factors which regulate antibody responses is specific antibody already present in the circulation. Circulating antibody will bind injected antigens and, depending on the relative amounts of antibody and antigen, may either inhibit or augment the antibody response. This project will utilize in vitro culture systems to examine the augmenting effects of antibody in the form of antigen-antibody complexes. Lymphocyte-separation techniques will be used to find out which lymphocyte population or subpopulation is responsible for the augmented responses and which cell-surface receptors are involved. Data from other laboratories suggest that certain components in the complement system are necessary for thymus-dependent antibody responses. We have demonstrated that antigen-antibody complexes stimulate normal lymphocytes to proliferate in vitro if complement is present. This system provides a unique model for examining the role of complement components in lymphocyte stimulation and antibody responses. Using purified complement components we will determine which components actually participate in antibody responses and whether they modulate the augmented responses to antigen-antibody complexes. Cell-separation techniques will allow determination of the lymphocyte subsets and the particular receptors which are affected through the activity of complement. The understanding of the regulatory action of antibody and complement will contribute to a better understanding of how lymphocytes are stimulated and provide an approach to therapy for immunodeficiency and lymphoproliferative diseases.